本文選題：腺苷酸活化蛋白激酶 + 腫瘤壞死因子��； 參考：《基因組學(xué)與應(yīng)用生物學(xué)》2017年04期

【摘要】：探討腺苷酸活化蛋白激酶(AMP activated protein kinase,AMPK)激活劑A-769662對腫瘤壞死因子α(tumor necrosis factor alpha,TNF-α)誘導(dǎo)的爆發(fā)性肝損傷中肝細(xì)胞凋亡的影響及機(jī)制。本研究在雄性BALB/c小鼠經(jīng)腹腔內(nèi)注射腫瘤壞死因子α(tumor necrosis factor alpha,TNF-α)及D氨基半乳糖胺(D-galactosamine,D-Gal),誘導(dǎo)爆發(fā)性肝炎模型。實(shí)驗(yàn)分為4組:正常對照組、A-769662單獨(dú)處理組、模型組和A-769662干預(yù)組。采用比色法檢測血漿轉(zhuǎn)氨酶活性及肝組織中caspase-8、caspase-9、caspase-3的相對活性,Western blotting法檢測肝組織中激活型caspase-3蛋白水平,TUNEL法檢測肝細(xì)胞凋亡,HE染色觀察肝組織病理變化,并記錄各組小鼠生存情況。A-769662干預(yù)抑制了TNF-α/D-Gal誘導(dǎo)的肝組織中caspase-8、caspase-9、caspase-3的活性和激活型caspase-3蛋白表達(dá)水平的升高,顯著減少肝細(xì)胞凋亡數(shù)目,明顯下調(diào)血漿中天冬氨酸氨基轉(zhuǎn)氨酶(aspartate transaminase,AST)與丙氨酸氨基轉(zhuǎn)氨酶(alanine transaminase,ALT)水平,減輕肝組織病理學(xué)改變,提高小鼠生存率。AMPK激活劑A-769662在TNF-α誘導(dǎo)的爆發(fā)性肝損傷中,可發(fā)揮抗凋亡保護(hù)效應(yīng),這可能是其在保肝效應(yīng)的新機(jī)制。
[Abstract]:To investigate the effect and mechanism of AMP activated protein kinase- AMPK activator A-769662 on hepatocyte apoptosis induced by tumor necrosis factor alpha-TNF- 偽. In this study, the male BALB/c mice were injected intraperitoneally with TNF- 偽 and D-galactosamine D-Galan to induce explosive hepatitis. The experiment was divided into 4 groups: normal control group A-769662 treatment group, model group and A-769662 intervention group. The activity of plasma aminotransferase and the relative activity of caspase-8 caspase-9 caspase-3 in liver tissue were detected by colorimetric assay. Western blotting assay was used to detect the level of activated caspase-3 protein in liver tissue. Tunel method was used to detect the apoptosis of hepatocytes and HE staining was used to detect the pathological changes of liver tissue. The survival status of mice in each group was also recorded. A-769662 intervention inhibited the increase of caspase-8 caspase-9 caspase-3 activity and the expression of activated caspase-3 protein in liver tissue induced by TNF- 偽 / D-Gal, and significantly reduced the number of hepatocyte apoptosis. The levels of aspartate transaminase (AST) and alanine transaminase (alanine transaminase) in plasma were significantly down-regulated, and liver histopathological changes were alleviated, and the survival rate of mice was increased by AMPK activator A-769662 in TNF- 偽 induced liver injury. This may be a new mechanism in protecting liver.
【作者單位】： 重慶醫(yī)科大學(xué)病理生理學(xué)教研室;重慶文理學(xué)院校醫(yī)院;重慶醫(yī)科大學(xué)干細(xì)胞與組織工程研究室;
【基金】：國家自然科學(xué)基金項(xiàng)目(81370179)資助
【分類號】：R575

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